Activation of the PI3K/Akt pathway is essential for the survival of Brucella melitensis 16M in vitro and in vivo

Brucellosis is a zoonotic pathogen that causes both animal and human diseases. brucella pathogenesis depends on the bacterial ability of inhibiting apoptosis and establishes a replicative niche inside host cells. the pi3k/akt pathway regulates various cellular activities (cell growth,survival,and apoptosis). however,the role of the pi3k/akt pathway in the survival of 16m in raw264.7 macrophages remains largely unknown. in our report,we demonstrated that the pi3k/akt pathway was activated by 16m in raw264.7 macrophages. we found that 16m infection induced the phosphorylation of both thr-308 and ser-473 of akt in a time-dependent manner. this phosphorylation was inhibited by ly in a dosedependent manner. inhibition of pi3k/akt with ly significantly reduced the internalisation and replication of 16m and induced 16m-dependent inhibition of apoptosis,and induced th1 and proinflammatory responses both in vitro and in vivo and protected mice against 16m infection. these results indicated that the pi3k/akt pathway plays an important role in 16m survival both in vitro and in vivo,which will help to unravel the pathogenic mechanisms of 16m. © 2014 pvj.